Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis

Nat Med. 2011 Sep 25;17(10):1283-9. doi: 10.1038/nm.2457.


Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorouracil, which are routinely prescribed in the adjuvant treatment of people with CRC. The survival and response to chemotherapy of subjects with MSI CRCs was associated with the tumor expression level of HSP110ΔE9. HSP110 may thus constitute a major determinant for both prognosis and treatment response in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Blotting, Western
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • DNA Primers / genetics
  • Fluorescent Antibody Technique
  • Fluorouracil
  • HSP110 Heat-Shock Proteins / genetics
  • HSP110 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunoprecipitation
  • Microsatellite Instability
  • Mutation / genetics
  • Organoplatinum Compounds
  • Oxaliplatin
  • Plasmids / genetics
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Regression Analysis
  • Transfection


  • Antineoplastic Agents
  • DNA Primers
  • HSP110 Heat-Shock Proteins
  • Organoplatinum Compounds
  • Oxaliplatin
  • Fluorouracil